Project 2: Analysis of Skeletal Muscle Function in Aging Mice. The purpose of this project is to provide measurements of age-sensitive traits from skeletal muscles of mice for studies of genetic linkage and biomarker validation and to investigate metabolic mechanisms underlying the increased fatiguability of muscles in old mice. The Program Project primary addresses Program-wide working hypotheses that direct studies to seek evidence for (i) correlations across organ systems in the extent of the accumulation of age-related changes, and (ii) the existence of polymorphic genetic loci that lead to relatively rapid aging. Deficits observed in skeletal in skeletal muscles of aging mice include decreases in mass, maximum isometric force, and resistance to fatigue. Project 2 will contribute to the overall goals of the Program Project, by providing structural, functional, and metabolic data from skeletal muscles of genetically heterogeneous female mice. These data will be examined by the Data Analysis Core along with data from the other Projects and the genotypic information from each mouse to test rigorously the Program's working hypotheses. In addition, Project 2 has aims related to our own interests in the biology of skeletal muscles in aging animals. Increased fatiguability is one of the primary contributors to physical frailty in the elderly. The fatiguability of individual skeletal muscle is assessed through measurements of sustained power during prolonged contractile activity. The ability of muscles in old animals to sustain power is significantly impaired compared with that of muscles in young animals. Mechanisms underlying these functional deficits have not been studied in aging mice. The working hypothesis is that the decreased ability of isolated muscles in old mice to sustain power during repeated contractions is due to altered substrate utilization. The large data sets generated by Project 2 will be used to seek relationships between the ability of a muscle to sustain power during contractile activity, the ability of the muscle to utilize substrates, and the animal;s level of voluntary activity. The development of these relationships will contribute significantly to our understanding of the increasing physical frailty observed with aging.